Quinoline derivatives are one of the most important heterocyclic scaffolds, which occur in various natural products, bioactive compounds and pharmaceuticals, as well as a key part for the synthesis of antibacterial, Alzheimer agents, anticancer agents, and antimalarial drugs. Because of such significance much attention has been paid to the synthesis of substituted quinolines in organic chemistry since the late 1800s. In the last few decades, a number of methods have been developed for quinoline synthesis, but many of them rule out their general application due to harsh reaction condition and poor regioselectivity. For the direct synthesis of quinoline derivatives from their commercially available starting materials few reports are there, but in most of the case 2-substituted quinoline derivatives are reported. Synthesis of 3-functionalized quinoline derivatives are pharmaceutically very important, but so far, there are very few reports for the synthesis of 3-substituted quinoline derivatives and all them are multistep process.
Article titled, “N-Bromosuccinimide-Mediated Radical Cyclization of 3-Arylallyl Azides: Synthesis of 3-Substituted Quinolines” by Wang et. al in Adv. Synthesis & Catalysis (2015), 357(1), 221-226 reports that visible light irradiation of N-bromosuccinimide serves as an effective means to convert methyl 2-(azidomethyl)-3-arylpropenoates and 2-(azidomethyl)-3-arylacrylonitriles to the corresponding iminyl radicals via α-hydrogen abstraction and subsequent extrusion of dinitrogen. Thus formed iminyl radicals then undergo intramolecular ortho attack on the aryl ring, affording methyl quinoline-3-carboxylates and quinoline-3-carbonitriles respectively.
S. C. BASAK ET AL: “Quantitative structure-activity relationship studies of antimalarial compounds from their calculated mathematical descriptors”, SAR AND QSAR IN ENVIRONMENTAL RESEARCH, vol. 21, no. 1-2, 1 Jan. 2010 (2010 Jan. 1), pages 103-125, XP055285631, GB ISSN: 1062-936X, DOI: 10.1080/10629360903568614 page 106, compound 7 describes a wide range of mathematical descriptors that can be calculated without the use of any other experimental data except molecular structure were used to develop models to predict binary (+/−) antimalarial activity of a set of 86 4 (1H)-quinolones in two strains of parasite: D6 and TM90-C2B (chloroquine and atovaquone susceptible). The quantitative structure-activity relationship for each strain was of high quality and showed good ability in predicting activity versus inactivity when applied to a data set containing well known antimalarial drugs.
SCOTT D A ET AL: “Identification of 3-amido-4-anilinoquinolines as potent and selective inhibitors of CSF-1R kinase”, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, PERGAMON, AMSTERDAM, NL, vol. 19, no. 3, 1 Feb. 2009 (2009 Feb. 1), pages 697-700, XP025925797, ISSN: 0960-894X, DOI: 10.1016/J.BMCL.2008.12.046 [retrieved on 2009 Jan. 31] page 698, compounds 32-33, describes 3-Amido-4-anilinoquinolines as potent and highly selective inhibitors of CSF-1R. Their synthesis and SAR is reported, along with initial efforts to optimize the physical properties and PK through modifications at the quinoline 6- and 7-positions.
CN 101 239 946 A (QINGYUN LING [CN]) 13 Aug. 2008 (2008 Aug. 13) CAPLUS-No: 24030-79-3 describes the invention discloses a preparing method of deccox, which uses cheap pyrocatechol as material to obtain deccox products with good quality and low cost by diethoxylation, nitration, alkali hydrolysis, decyloxylation, reduction, condensation, ring closing and hydrolyzation. Compared with the prior art, materials such as 3,4-dihydroxynitrobenzene or catechol ethylether, which are expensive and not easy to buy, are replaced by chemical materials, such as plate caustic soda, pyrocatechol, diethyl sulfate, glacial acetic-acid, nitric acid, glycol monoethyl ether, potassium hydroxide, bromodecane, phosphorus oxychloride, ethoxymethylene, sodium hydroxide, etc., which are cheap and easy to obtain, the reaction condition is gentle, the integration cost is 50% lower than that of the prior art.
MARRERO-PONCE Y ET AL: “Ligand-Based Virtual Screening and in Silica Design of New Antimalarial Compounds Using Nonstochastic and Stochastic Total and Atom-Type Quadratic Maps”, JOURNAL OF CHEMICAL INFORMATION AND MODELING, AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC, US, vol. 45, no. 4, 1 Jan. 2005 (2005 Jan. 1), pages 1082-1100, XP008114058, ISSN: 1549-9596, DOI: 10.1021/CI050085T [retrieved on 2005 Jun. 9] CAPLUS-No: 80061-37-6.
WO 02/092571 A1 (ASTRAZENECA AB [SE]; LARSSON JOAKIM [SE]; SJOE PETER [SE]) 21 Nov. 2002 (2002 Nov. 21) CAPLUS-No: 26893-14-1; 476193-56-3; 476193-58-5 describes the novel compounds of formula (IA), which are JAK3 Kinase inhibitors, methods for their preparation and pharmaceutical compositions comprising them.
WO 02/44166 A1 (ASTRAZENECA AB [SE]; ASTRAZENECA UK LTD [GB]; BOYLE FRANCIS THOMAS [GB) 6 Jun. 2002 (2002 Jun. 6) CAPLUS-No: 307353-90-8 307353-91-9 describes the invention provides a compound of Formula (Ia) or a pharmaceutically acceptable salt, pro-drug or solvate thereof. The invention also provides a process for the preparation of a compound of Formula (Ia), pharmaceutical compositions of a compound of Formula (Ia) and methods for the treatment or prevention of cancer comprising administering an effective amount of a compound of Formula (Ia).
JP H10 330377 A (KYOWA HAKKO KOGYO KK) 15 Dec. 1998 (1998 Dec. 15) CAPLUS-No: 26893-14-1; 219324-58-0 describes the subject new compound having a potent inhibitory action for cell adhesion, and having excellent anti-inflammatory activity, antiallergic activity, suppressing activity of a rejection on an organ transplantation and suppressing activity of cancer metastasis. SOLUTION: This piperidine derivative is a compound of formula I [R<1> is a (non)substituted lower alkyl, hydroxy, etc.; R<2> is H, carboxyl, etc.; R<3> is H or a lower alkyl; R<4> is H, a lower alkoxy, etc.; X<1>-X<2> is N═N, N═C(R<5>), (R<5> is H, amino, etc.), etc.; Y<1>-Y<2>-Y<3> is ═N—C—(R<8>)=N, ═N—N═C—(R<8> A), (R<8>, R<8> A are each H, a halogen, etc.), etc.; Z<1>, Z<2> are each H, nitro, etc.; (n) is 0-2] or a salt thereof, e.g. 1-[1-(4-chloro-6,7-dimethoxy-1-phthalazinyl)-4-piperidinyl]-2,3-dihydro-5-methyl-1H-benzimidazol-2-one. The compound of the formula I is obtained by e.g. reacting a compound of formula II with a compound of formula III (Hal is chlorine, bromine or iodine) in a solvent such as methanol.    PURI S K ET AL: “Quinoline esters as potential antimalarial drugs: effect on relapses of Plasmodium cynomolgi infections in monkeys”, TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, ELSEVIER, GB, vol. 84, no. 6, 1 Nov. 1990 (1990 Nov. 1), pages 759-760, XP023096499, ISSN: 0035-9203, DOI: 10.1016/0035-9203(90)90066-N [retrieved on 1990 Nov. 1] page 759, compound WR194905 describes that two compounds of the quinoline ester series, WR 197236 (6-butyl-4-hydroxy-3-methoxycarbonyl-7-β-phenoxyethoxyquinoline) and WR 194905 (4-acetoxy-6-decyloxy-7-isopropoxy-3-methoxycarbonylquinoline), exhibit anti-relapse activity against sporozoite-induced Plasmodium cynomolgi B infections in rhesus monkeys. Both the compounds have been found to be curative when given intramusculary in 7 daily doses of 15 mg/kg, and no relapses were observed during the observation period of 120 d.

Article titled, “Iodine-Mediated Intramolecular Electrophilic Aromatic Cyclization in Allylamines: A General Route to Synthesis of Quinolines, Pyrazolo[4,3-b]pyridines, and Thieno[3,2-b]pyridines” by Batchu, Harikrishna; Bhattacharyya, Soumya; Batra, Sanjay in Org. Letters (2012), 14(24), 6330-6333 reports the synthesis of aromatic ring annulated pyridines from suitably substituted primary allylamines via intramolecular electrophilic aromatic cyclization mediated by molecular iodine under mild conditions is described.

Article titled, “Using Morita-Baylis-Hillman acetates of 2-azido benz-aldehydes for the synthesis of 2-alkoxy-3-cyanomethyl quinolines and alkyl quinoline-3-carboxylates” By Kim et. al in Journal of Heterocyclic Chemistry (2011), 48(4), 965-972 reports a simple method for the synthesis of several 2-alkoxy-3-cyanomethyl quinolines and alkyl quinoline-3-carboxylates, using iminophosphorane-mediated cyclization reactions of 3-(2-azidophenyl)-2-cyanomethylpropenoates and 3-(2-azidophenyl)-2-nitromethylpropenoates. These compounds were obtained from the Morita-Baylis-Hillman acetates of 2-azidobenzaldehydes using potassium cyanide or sodium nitrite, resp.
Article titled, “Quinolines from Morita-Baylis-Hillman acetates of 2-azidobenzaldehydes” by Han et. al in Tetrahedron (2009), 65(46), 9616-9625 reports a simple method for synthesizing several 2-alkoxy-3-arylsulfinylmethylquinolines using an aza-Wittig type reaction of 3-(2-azidophenyl)-2-(arylsulfinylmethyl) propenoates, which were readily obtained from the Morita-Baylis-Hillman acetates of 2-azidobenzaldehydes.
Article titled, “Synthesis of quinoline N-oxides from the Baylis-Hillman adducts of 2-nitrobenzaldehydes: Conjugate addition of nitroso intermediate” by Lee, Ka Young; Kim, Seung Chan; Kim, Jae Nyoung in Bulletin of the Korean Chemical Society (2005), 26(7), 1109-1111 reports a facile one-pot method for the prepn. of quinoline N-oxides, e.g. I, from the Baylis-Hillman adducts of orthonitrobenzaldehydes via the conjugate addn. of the nitroso functionality as the key step. This method can be applied for the regioselective synthesis of 2 hydroxyquinoline derivatives.

Article titled, “Synthesis of 3-Substituted Quinolines via Transition-Metal-Catalyzed Reductive Cyclization of o-Nitro Baylis-Hillman Acetates” by O'Dell et. al in Journal of Organic Chemistry (2003), 68(16), 6427-6430 reports reductive cyclization of o-nitro-substituted Baylis-Hillman acetates by carbon monoxide, catalyzed by [Cp*Fe(CO)2]2, gives moderate to good yields of 3-substituted quinolines.

Article titled, “Rh(I)-Catalyzed Coupling Cyclization of N-Aryl Trifluoroacetimidoyl Chlorides with Alkynes: One-Pot Synthesis of Fluorinated Quinolines” by Hideki Amii, Yosuke Kishikawa and Kenji Uneyama in Org. Lett. 3, 1109-1112 (2001) reports rhodium-catalysed non-directed C—H activation strategy with the carbonylation reaction in an auto tandem manner.

Article titled, “Copper-Catalyzed Synthesis of Substituted Quinolines via C—N Coupling/Condensation from ortho-Acylanilines and Alkenyl Iodides” by Lingkai Kong, Yuanyuan Zhou, He Huang, Yang Yang, Yuanyuan Liu and Yanzhong Li in J. Org. Chem., 2015, 80 (2), pp 1275-1278 reports an efficient cascade copper-catalyzed intermolecular Ullmann-type C—N coupling/enamine condensation reaction, in which ortho-acylanilines and alkenyl iodides converted to multisubstituted quinolines in good to excellent yields.
Article titled, “Iron-catalyzed cascade reaction of ynone with o-aminoaryl compounds: a Michael addition-cyclization approach to 3-carbonyl quinolines” by Hongfeng Li, Xiaolei Xu, Jingyu Yang, Xin Xie, He Huang, Yanzhong Li in Tetrahedron Letters, Volume 52, Issue 4, 26 Jan. 2011, Pages 530-533 reports an efficient iron-catalyzed cascade Michael addition-cyclization of o-aminoaryl compounds including o-aminoaryl aldehydes, o-aminoaryl ketones, and o-aminobenzyl alcohols with ynones for the synthesis of 3-carbonyl quinolines.

Article titled, “Palladium catalyzed synthesis of 2-trifluoromethylquinolines through a domino Sonogashira-alkyne carbocyclization process” Zixian Chen et. al in Chem. Commun., 2010, 46, 2145-2147 reports a new, rapid and high-yielding method to prepare 3,4-disubstituted 2-trifluoromethylquinolines by a palladium catalyzed tandem Sonogashira-alkyne carbocyclization of β-trifluoromethyl 1-enaminoketones with arynes.
Article titled, “Practical and Simple Synthesis of Substituted Quinolines by an HCl-DMSO System on a Large Scale: Remarkable Effect of the Chloride Ion” by Shin-ya Tanaka, Makoto Yasuda, and Akio Baba J. Org. Chem., 2006, 71 (2), pp 800-803 reports A variety of substituted quinolines synthesized from imines and enolizable carbonyl compounds under aerobic conditions.
“Antiviral quinolines” By Kaminsky, Daniel in Fr. Demande (1969), FR 2002888 19691031 relates to Compds. of formula I {R1=H, Cl, OH, SH, or SEt; R2=H, CO2Et, CO2H, CN, or CHO; R3, R4, R5=H, Br, Cl, F, CN, OMe, OEt, SMe, OAc, Me, or CF3; or (R4R5=) OCH2O (A) or O(CH2 quinolines with in vivo antiviral properties)20 (B)} have esp. useful in the treatment of respiratory infections.
Article titled, “Rhodium(II)-catalyzed nondirected oxidative alkenylation of arenes: arene loading at one equivalent” by HU Vora et al. published in Angewandte Chemie International Edition, Volume 53, Issue 10, pages 2683-2686, Mar. 3, 2014 reports a bimetallic Rh(II) catalyst promoted the C—H alkenylation of simple arenes at 1.0/equivalent without the use of a directing group. A phosphine ligand as well as cooperative re-oxidation of Rh(II) with Cu(TFA)2 and V2O5 proved essential in providing monoalkenylated products in good yields and selectivities, especially with di- and trisubstituted arenes.
Article titled, “Rh catalyzed C—H activation and oxidative olefination without chelate assistance: on the reactivity of bromoarenes” by F W Patureau et al. published in Org. Lett., 2011, 13 (24), pp 6346-6349 reports a Rh catalyzed, non-chelate-assisted C—H activation/oxidative olefination reaction of bromoarenes has been discovered, in which the latter ones seem to act as a substrate, terminal oxidant, and catalyst modifier.
Article titled, “Carbonylations of alkenes with CO surrogates.” By L. Wu, Q. Liu, R. Jackstell, M. Beller in Angew. Chem. Int. Ed. 2014, 53, 6310 reports Alkene carbonylation reactions are important for the production of value-added bulk and fine chemicals. Nowadays, all industrial carbonylation processes make use of highly toxic and flammable carbon monoxide. In fact, these properties impede the wider use of carbonylation reactions in industry and academia. Hence, performing carbonylations without the use of CO is highly desired and will contribute to the further advancement of sustainable chemistry. Although the use of carbon monoxide surrogates in alkene carbonylation reactions has been reported intermittently in the last 30 years, only recently has this area attracted significant interest. This review summarizes carbonylation reactions of alkenes using different carbon monoxide surrogates.
Article titled, “Bicyclic compounds as ring-constrained inhibitors of protein-tyrosine kinase p56lck” by T. R. Burke, Jr., B. Lim, V. E. Marquez, Z.-H. Li, J. B. Bolen, I. Stefanova, I. D. Horaks in J. Med. Chem., 1993, 36, 425 reports a process to prepare inhibitors of the lymphocyte protein-tyrosine kinase p56lck. Using the known p56lck inhibitor 3,4-dihydroxy-alpha-cyanocinnamamide (4) as a lead compound, bicyclic analogues were designed as conformationally constrained mimetics in which the phenyl ring and vinyl side chain of the cinnamamide are locked into a coplanar orientation. Bicyclic analogues were prepared using the naphthalene, quinoline, isoquinoline, and 2-iminochromene ring systems and examined for their ability to inhibit autophosphorylation of immunopurified p56lck. The most potent analogues were methyl 7,8-dihydroxyisoquinoline-3-carboxylate (12) (IC50=0.2 microM) and 7,8-dihydroxyisoquinoline-3-carboxamide (13) (IC50=0.5 microM). Inhibition by 12 was not competitive with respect to ATP. These compounds may represent important new structural motifs for the development of p56lck inhibitors.
Article titled, “New Efficient Synthesis of 3-Carboxylquinolines” by S. Kirankumar, D. Rambabu, N. Chandra Sekhar, ASG. Prasad and M. V. Basaveswara Rao in Journal of the Korean Chemical Society, 2012, Vol. 56, No. 3 reports one pot, acid catalyzed, new methodology for the fast and efficient synthesis of highly functionalized quinoline derivatives.
                US20140275548 A1 provides a chemical entity of Formula (I)        

wherein R1, R2, R3, Y, and n have any of the values described herein and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies, detection and imaging techniques, and radioactive treatments; and therapies, including inhibiting MAO, and MAO-B selectively, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating treating peripheral disorders (including obesity, diabetes, and cardiometabolic disorders) and their associated co-morbidities.
Therefore, there is need in the art to develop a one step and easy to operate method for the synthesis of 3-substituted quinoline with more effective yield. Accordingly, a desirable way to encounter 3-substituted quinoline derivatives from the commercially available aniline derivatives using electron deficient alkvne and paraformaldehyde as a CO procurator is disclosed. In the reaction, use of paraformaldehyde as a CO proxy leads to the quinoline products with more effective yield. Moreover this one pot sequential method only proceeds by using water as a solvent, which is a green approach for synthetic purpose.